Mycolic Acid Inhibitors

Tuberculosis, caused by Mycobacterium tuberculosis, infects 10 million people annually while causing 1.5 million annual deaths. M. tuberculosis possesses a cell wall composed of mycolic acids that are impervious to most drugs. Isoniazid and ethambutol are two mycolic acid inhibitors effective against sensitive strains of M. tuberculosis. For isoniazid, mycolic acid inhibition can be assayed using \({ }^{14}\) C-labeled n-fatty acids that act as mycolic acid precursors, following the extraction of products and visualization using thin-layer chromatography. Ethambutol inhibits the enzyme arabinosyl transferase, which are required for cell wall assembly. This can be visualized using by tracing the uptake and metabolism of \({ }^{14}\) C-labeled glucose into the mycolic-acid-containing cell wall. Mutations within the KatG and InhA genes are responsible for isoniazid resistance. Mutations within the embCAB operon are responsible for ethambutol resistance.